The innate immune system serves as a first line of defense against viral infections. Germline encoded pattern recognition receptors detect pathogens and promote innate immune responses, including activation of type I interferons (IFNs) and stimulation of antiviral genes. In addition to limiting infections, innate immunity is required to activate humoral responses and to develop long-term protection via adaptive immune response. Dysregulation of IFN signaling is detrimental to the host, resulting in events such as cytokine storms during infections or autoimmune disorders.

In my laboratory, we use a multidisciplinary research program that spans length and time scales to address this question by characterizing the molecular mechanisms of initial interactions at the host-pathogen interface. Using this information, we expect to develop a framework to manipulate viruses by modulating virulence (less virulent) in order to gain insight into immune mechanisms that are at play during these critical time points. Our current efforts are aimed toward defining the molecular basis for viral hemorrhagic fever (VHF) at the host-viral interface. VHF is a complex multivariable challenge with contributions from the virus and from the host dictating the outcome. We have begun a series of studies to understand the viral components, host factors and their interactions between each other. Below I briefly describe recent and recently completed studies that provide the experimental framework for us to examine these questions.